Triploidy

In triploidy each chromosome occurs 3 times for a total chromosome number of 69. Approximately 1% of clinical conceptions are triploidy with the majority miscarrying in the early part of the 1st trimester1. The reported prevalence of triploidy decreases from 1/1,500 at 10-14 weeks gestation2 to 1/10,000 at term3.

Triploidy may be from either paternal or maternal origin. The 3 possible karyotypes are: 69, XXX; 69, XXY; and 69, XYY. Approximately 75% of cases are of paternal origin, usually from the fertilization of an ovum by two haploid sperm (dispermy). The production of sperm and eggs requires meiosis, a specific type of cell division. Before meiosis I, a diploid cell replicates its DNA. In meiosis I the DNA divides so that each daughter cell receives 2 identical strands of DNA. During meiosis II the chromosome separates into single strands before division into 4 cells, each haploid, with one chromosome of each pair. Hence, triploidy can also result from a failure of division of either meiosis I or II in the father3.

Triploidy of maternal origin (digyny) is due to a failure of division during meiosis I or II3. Digynic triploidy is more commonly identified in the fetal period than diandric triploidy4. The documentation of a few livebirths of digynic triploidy suggests that they have a survival advantage over diandric triploidy5.

The prevalence of 69XYY in pre-implantation genetic studies (8.7%) is 12 times higher than in clinical pregnancies (0.74%). This suggests that an excess paternal contribution to the embryo adversely affects development6.

Since the formation of a triploid embryo is a random event, the couple's future reproductive potential would not be affected.

First trimester growth restriction has been described with triploidy7. Asymmetry between the head and abdomen may also be apparent during the 1st trimester. The deficit in triploidy 1st trimester trunk and head volume is 45%, in contrast to a 15% reduction in the crown-rump length. Hence, the trunk and head are decreased even after correcting for the crown-rump length8. Congenital anomalies have been detected on 1st trimester ultrasound examinations of triploidy fetuses9.

With 1st trimester diandric triploidy there may be a large cystic appearing placenta (Fig. 1). The 1st trimester nuchal translucency (NT) is increased (Fig. 2). Maternal serum β-hCG is significantly increased and PAPP-A is slightly decreased. Digynic triploidy has a small placenta, a normal NT and significantly lower β-hCG and PAPP-A.

The differences in triploidy phenotype are due to genomic imprinting with the extra paternal set of chromosomes leading to an over-expression of hCG2. Hence, the characteristic biochemistry is what permits identification of triploidy with a 1st trimester genetic screen. The use of the combined algorithms for trisomy 21, 18, and 13, detects approximately 85% of 1st trimester triploidy fetuses with a 3% false positive rate10.

The first trimester biochemical markers are not applicable to twin pregnancies. However, 1st trimester growth restriction and a small placental volume can be used to suggest chorionic villus sampling of one fetus in a twin gestation11.

McFadden et al4 have reported that the 2nd trimester triple screen results with digynic triploidy (low levels of hCG and unconjugated estriol) is interpreted by the established computer programs as an increased risk for trisomy 18. The elevated hCG and AFP in diandric triploid fetuses may be due to the presence of a partial hydatidiform mole, or the generally increased placental mass with diandric triploid fetuses who do not have a mole.

71.4% of 2nd trimester fetuses with triploidy present with asymmetric intrauterine growth restriction10. Characteristically, there is a marked discrepancy in the head to abdomen ratio that results from a more severe lag in abdominal circumference, in contrast to the head circumference (relative macrocephaly) (Fig. 3).

Triploidy fetuses have a plethora of fetal anomalies that have been described involving almost every organ system (Table I). This list illustrates the breadth of the triploidy spectrum. However, there is not a single anomaly that would be considered pathognomonic for triploidy.

Respiratory

Gastrointestinal

Genitourinary

Renal cystic dysplasia

Renal agenesis

Renal hypoplasia

Ambiguous genitalia

Skeletal/Limbs

Syndactyly (3rd & 4th digits)

Clubbed feet

Hitchhiker's toe

Kyphoscoliosis

2 Vessel Umbilical Cord

Central nervous system anomalies are the most common malformations associated with triploidy (Fig. 4), with a frequency of approximately 50%. Cardiac anomalies have been detected in 31.4% of triploid fetuses; ventriculoseptal and atrioseptal defects (Fig. 5) are the most common2. Truncus anteriosis, Ebstein's anomaly and aortic stenosis have also been described12. Omphalocele and gastroschisis are present in 10-18% of triploid fetuses. 86% of 2nd trimester triploid fetuses will have more than one major structural malformation (Figs. 6-9)6.

Approximately 40-60% of triploid fetuses have oligohydramnios and an additional 5% have polyhydramnios13. Due to the frequent presence of oligohydramnios, the sonographic detection rate of congenital anomalies is less than would be expected with a normal amniotic fluid volume.

In 7%14 to 15%6 of 2nd trimester triploidy cases, there are not any major congenital anomalies detected on an extended fetal anatomic survey15. Interval 2nd trimester growth of the biparietal diameter has been described as normal in some cases15.

As previously stated, placental abnormalities are associated with triploidy10,15,16,17. The finding of triploidy in a molar pregnancy is associated with a small risk for persistent trophoblastic disease. Complete moles contain only paternal chromosomes and have a 15-25% risk for persistent trophoblastic disease18.

Early onset (16-24 weeks) preeclampsia is an acknowledged complication of triploidy with a partial mole16.

The differential diagnosis for the sonographic findings associated with triploidy include: 1) a normal fetus with growth restriction and a small placenta; 2) a complete mole with a co-existent fetus; 3) trisomy 13; 4) trisomy 18; and 5) a normal fetus with placental mesenchymal dysplasia (PMD).

Placental mesenchymal dysplasia is characterized by an enlarged hydropic placenta with multiple cysts. Sonographically this is indistinguishable from a mole or partial mole. Unlike a molar placenta, trophoblastic proliferation is absent. PMD is associated with a predominance of female fetuses. Other fetal complications associated with PMD include polyhydramnios, intrauterine growth restriction, intrauterine fetal demise and prematurity19.

Summary

Second trimester intrauterine growth restriction, marked asymmetry between the head and abdomen with relative macrocephaly and a cystic appearing placenta are the triad of sonographic findings that are highly suggestive of triploidy. Since several diseases overlap phenotypically with triploidy, early detection and karyotypic confirmation are essential.